This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Located in the perivascular space of cerebral microvessels, perivascular macrophages are uniquely situated at the interface between brain parenchyma and blood vessels. Connections between the nervous and immune systems are mediated in part through these cells that are ideally located to sense perturbations in the periphery and are turn over by cells entering the CNS from the circulation. It has become clear that unique subsets of brain macrophage exist in normal and SIV and HIV infected brain, and perivascular macrophages and cells similar to perivascular macrophages in the meninges and choroids plexus play a central role in lentiviral pathogenesis. Common to all these cell populations is their replacement within the CNS by monocytes. Studies of SIV infected non human primates and HIV infected humans underscore the importance of HIV-infected and/or activated monocytes, which traffic to the central nervous system (CNS) the potentially drive the blood-brain barrier damage and may cause neuronal injury.